Oxidative stress in Systemic Sclerosis

Simonini, Gabriele; Cerinic, Marco Matucci; Generini, Sergio; Zoppi, M.; M, Anichini; Cesaretti, Claudia; Pignone, Alberto Moggi; Falcini, Fabio; Lotti, Torello; Cagnoni, M

doi:10.1007/978-1-4615-5097-6_10

Cited by 38 publications

(33 citation statements)

References 43 publications

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“…In addition, the autoantibody response has been suggested to be the immune marker of protein fragmentation induced by reactive oxygen species (17). SSc patients have been shown to have elevated levels of malondialdehyde, diene conjugates, and clastogenic plasma factors (9,18,19), and a reduced micronutrient antioxidant status compared with controls (20). However, these techniques have important limitations, as recently reviewed by Moore and Roberts (21).…”

Section: Discussionmentioning

confidence: 99%

Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders

Cracowski

Marpeau

Carpentier

et al. 2001

Arthritis & Rheumatism

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Section: Discussionmentioning

confidence: 99%

Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders

Cracowski

Marpeau

Carpentier

et al. 2001

Arthritis & Rheumatism

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“…These 2 elements can thus overlap, jeopardizing the integrity of the vessel wall. In genetically predisposed SSc patients, characterized by ischemia and oxidative stress, 68 with raised levels of LDL undergoing oxidation, triggering vessel wall inflammation, 69 the overlap with SSc-dependent endothelial injury creates a noxious loop involving the microcirculation and macrocirculation. In this scenario, pathogenetic factors participating in endothelial sufferance, such as anti-endothelial cell antibodies, dysfunction of the fibrinolytic and coagulation system, and an increase of circulating levels of homocysteine, soluble intercellular adhesion molecule-1, and CRP may contribute significantly to increased risk of developing accelerated macrovascular disease.…”

Section: Macrovascular Disease and Atherosclerosis In Systemic Sclerosismentioning

confidence: 99%

Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases

et al. 2005

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“…The mechanisms that determine the clinical manifestations of the disease remain unclear (2). Several reports have suggested that reactive oxygen species (ROS) are involved in the pathogenesis of SSc (3)(4)(5)(6)(7)(8)(9). Indeed, skin fibroblasts from SSc patients spontaneously produce large amounts of ROS that trigger collagen synthesis (7,10).…”

Section: S Ystemic Sclerosis (Ssc)mentioning

confidence: 99%

Selective Oxidation of DNA Topoisomerase 1 Induces Systemic Sclerosis in the Mouse

Servettaz¹,

Goulvestre²,

Kavian³

et al. 2009

The Journal of Immunology

178

184

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Systemic sclerosis (SSc) is a connective tissue disorder of great clinical heterogeneity. Its pathophysiology remains unclear. Our aim was to evaluate the relative roles of reactive oxygen species (ROS) and of the immune system using an original model of SSc. BALB/c and immunodeficient BALB/c SCID mice were injected s.c. with prooxidative agents (hydroxyl radicals, hypochlorous acid, peroxynitrites, superoxide anions), bleomycin, or PBS everyday for 6 wk. Skin and lung fibrosis were assessed by histological and biochemical methods. Autoantibodies were detected by ELISA. The effects of mouse sera on H 2 O 2 production by endothelial cells and on fibroblast proliferation, and serum concentrations in advanced oxidation protein products (AOPP) were compared with sera from patients with limited or diffuse SSc. We observed that s.c. peroxynitrites induced skin fibrosis and serum anti-CENP-B Abs that characterize limited SSc, whereas hypochlorite or hydroxyl radicals induced cutaneous and lung fibrosis and anti-DNA topoisomerase 1 autoantibodies that characterize human diffuse SSc. Sera from hypochlorite-or hydroxyl radical-treated mice and of patients with diffuse SSc contained high levels of AOPP that triggered endothelial production of H 2 O 2 and fibroblast hyperproliferation. Oxidized topoisomerase 1 recapitulated the effects of whole serum AOPP. SCID mice developed an attenuated form of SSc, demonstrating the synergistic role of the immune system with AOPP in disease propagation. We demonstrate a direct role for ROS in SSc and show that the nature of the ROS dictates the form of SSc. Moreover, this demonstration is the first that shows the specific oxidation of an autoantigen directly participates in the pathogenesis of an autoimmune disease. The Journal of Immunology, 2009, 182: 5855-5864. S ystemic sclerosis (SSc)4 is a connective tissue disorder of unknown etiology characterized by vascular hyperreactivity, fibrosis of skin and visceral organs, and immunological alterations, including a distinct pattern of autoantibodies in the sera (1). The mechanisms that determine the clinical manifestations of the disease remain unclear (2). Several reports have suggested that reactive oxygen species (ROS) are involved in the pathogenesis of SSc (3-9). Indeed, skin fibroblasts from SSc patients spontaneously produce large amounts of ROS that trigger collagen synthesis (7, 10). In addition, autoantibodies found in SSc patients against the platelet-derived growth factor receptor expressed on fibroblasts also induce the production of ROS (11). Recently, we have demonstrated that sera from patients with SSc could induce not only the production of ROS by endothelial cells but also the hyperproliferation of fibroblasts (6).However, no direct proof for the involvement of oxidative stress in SSc pathogenesis has been brought forth to date. Moreover, the origin and nature of the oxidative stress remain to be elucidated. Environmental factors, and in particular silica dust, may be involved, which generate hydroxyl radicals (OH⅐) (12...

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Oxidative stress in Systemic Sclerosis

Cited by 38 publications

References 43 publications

Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders

Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders

Accelerated Atherosclerosis in Autoimmune Rheumatic Diseases

Selective Oxidation of DNA Topoisomerase 1 Induces Systemic Sclerosis in the Mouse

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